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DNA damage increase in peripheral neutrophils from patients with rheumatoid arthritis is associated with the disease activity and the presence of shared epitope

1, 2, 3, 4, 5, 6, 7, 8

 

  1. Program of Basic & Applied Immunol., Faculty Medicine Ribeirão Preto (FMRP-USP), Univ. São Paulo; and Dept. Clinical & Toxicological Analysis, School of Pharmaceutical Sciences, Federal Univ. Rio Grande do Norte (UFRN), Natal, Rio Grande do Norte, Brazil.
  2. Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil.
  3. Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, Federal University of Rio Grande do Norte (UFRN), Natal, Rio Grande do Norte, Brazil.
  4. Division of Rheumatology, Faculty de Medicine, University of São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil.
  5. Division of Rheumatology, Faculty de Medicine, University of São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil.
  6. Division of Rheumatology, Faculty de Medicine, University of São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil.
  7. Program of Basic and Applied Immunology, and Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil.
  8. Program of Basic and Applied Immunology, and Department of Rheumatology, Faculty de Medicine de Ribeirão Preto (FMRP-USP), University of São Paulo Ribeirão Preto, São Paulo, Brazil.

CER9493
2017 Vol.35, N°2
PI 0247, PF 0254
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PMID: 27908303 [PubMed]

Received: 08/04/2016
Accepted : 02/09/2016
In Press: 14/11/2016
Published: 15/03/2017

Abstract

OBJECTIVES:
Neutrophils play a major role in rheumatoid arthritis (RA) pathogenesis. We aimed to evaluate if neutrophil DNA damage in RA patients is associated with the disease activity, autoantibodies status, carriage of the RA shared epitope (SE) and treatment.
METHODS:
DNA damage was assessed by alkaline comet assay in peripheral blood (77 patients and 55 healthy controls) and in 10 RA synovial fluid neutrophils. Evaluation of the respiratory burst of 30 patients with RA and 30 healthy controls was done.
RESULTS:
Compared to controls, RA patients exhibited increased neutrophil DNA damage. RA synovial fluid cells DNA damage was increased when compared to OA synovial fluids cells. In addition, our study shows that anti-TNF-α therapy reduces the frequency of DNA damage. Patients with simple or double dose of shared epitope presented a higher frequency of DNA damage compared to patients without the allele. Positive correlation was found between neutrophil DNA damage and DAS-28 and ROS production.
CONCLUSIONS:
Our results suggest that an increase of respiratory burst of neutrophils reflects the higher levels of DNA damage in neutrophils and a positive correlation between DNA damage and disease activity shows the importance of oxidative stress in the pathogenesis of RA.

Rheumatology Article